PROJECT SUMMARY ABSTRACT Epilepsy affects 2.2 million adults in the United States, with 1 in 26 people developing epilepsy at some point in their lives. Temporal lobe epilepsy (TLE) is the most common form of focal epilepsy as medial structures, and the hippocampus in particular, are prone to generating seizures. Selective temporal resection is effective in curing TLE in 74-80% of patients, but puts patients at risk of impaired memory functioning. To minimize the adverse impact of temporal lobe surgery on memory functioning, reliable pre-surgical guides are needed. Clinical functional magnetic resonance imaging (fMRI) provides reliable, noninvasive guidance of language functioning in the pre-surgical evaluation for epilepsy patients. FMRI of memory is also emerging as a useful technology to predict adult outcomes and new AAN Practice Guidelines indicate moderate (Level B) evidence for verbal memory fMRI in predicting verbal memory outcome, based on adult studies. However, no memory fMRI studies exist in children with epilepsy. We will fill this gap by developing memory fMRI tasks that examine how the functional anatomy of memory systems across development is affected by pediatric TLE. Our novel approach links neuropsychological assessment with fMRI and MRI at standard and high-resolutions, and through resting-state connectivity to characterize the developmental neural underpinnings of memory. The aims of this proposal are to determine potential reorganization of memory function in children with TLE: 1) at the whole brain level, 2) within the hippocampus, and 3) via connectivity. This project will establish an fMRI protocol for the presurgical evaluation of memory in children with TLE. This protocol will improve surgical intervention by establishing the optimal timing of surgery based on when critical windows for reorganization occur. The Principal Investigator, Leigh Sepeta, PhD, is a neuropsychologist specializing in pediatric and adult epilepsy, with a focus on fMRI for language and memory mapping in epilepsy. She has a strong background in neurodevelopment, neuropsychology, and epilepsy. The proposed training plan will build upon her existing knowledge and promote three goals: 1) to acquire expertise in advanced neuroimaging methods, 2) to develop skills in high-resolution neuroimaging, hippocampal anatomy, and hippocampal subregion analysis, and 3) to advance skills in biostatistical analysis. Dr. Sepeta has assembled a strong mentorship and consultant team including William D. Gaillard, M.D., William H. Theodore, M.D., Chandan Y. Vaidya, PhD and Susan Y. Bookheimer, PhD (secondary mentor). Their expertise in pediatric and adult epilepsy, neuroimaging, hippocampal functioning, and neuropsychology are an ideal match for Dr. Sepeta's proposed research and training plans. The research-training program Dr. Sepeta has designed for this K23 proposal will further her overall goal of transitioning to an independent investigator focused on neuropsychological and neuroimaging evaluation of memory in neurological disorders, such as epilepsy.